ABSTRACT
Dihydroartemisinin-piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett's correction) were 2 (-6 to 9) ms and 14 (7 to 21) ms, respectively. These small changes on the third day of treatment are similar to those observed elsewhere in the convalescent phase following antimalarial treatment with drugs known to have no cardiac effects and are therefore likely to result from recovery from acute malaria and not the treatment given. At therapeutic doses, DP does not have clinically significant effects on the electrocardiogram.
Subject(s)
Arrhythmias, Cardiac/chemically induced , Artemisinins/adverse effects , Artemisinins/therapeutic use , Electrocardiography , Malaria, Falciparum/drug therapy , Sesquiterpenes/adverse effects , Sesquiterpenes/therapeutic use , HumansABSTRACT
OBJECTIVE: To determine the pharmacokinetic properties of artemether and lumefantrine (AL) in pregnant women with recrudescent uncomplicated multi-drug resistant falciparum malaria. METHODS: Pregnant women who had recurrence of parasitaemia following 7 days supervised quinine treatment were treated with AL. Serial blood samples were taken over a 7-day period, and pharmacokinetic parameters were estimated. For lumefantrine, these data were compared in a population pharmacokinetic model with data from non-pregnant, mainly male adults with acute malaria. RESULTS: The pregnant women (five in the second trimester and eight in the third trimester) had lower concentrations of artemether, dihydroartemisinin and lumefantrine, and the elimination of lumefantrine in pregnant women was more rapid than reported previously in non-pregnant adults. CONCLUSION: Pregnancy is associated with reduced plasma concentrations of both artemether and lumefantrine. This is likely to be of therapeutic significance as plasma concentrations of lumefantrine, after elimination of artemether, are an important determinant of cure. Further studies are needed to determine the optimum dose regimen of artemether-lumefantrine in pregnancy.
